RESEARCH OBJECTIVES: 1. Identification, isolation, and characterization of initiation sites for DNA replication in mammalian cell DNA; 2. Definition of the relationship between cell cycling and expression of SV40 virus gene function; 3. Application of selective reversible inhibition of RNA polymerase II by DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) to studies of the synthesis of message-containing RNA of cells and viruses; and 4. Elucidation of the action of interferon and DRB on cell proliferation. These studies are designed to increase our understanding of the virus-cell interactions of simian virus 40 (SV40), adenovirus, and Rous sarcoma virus. The processes of cellular and viral DNA replication and RNA transcription, and of cell cycling will be investigated. The objective also is to define in detail the action of human fibroblast interferon on normal and transformed human cells. A wide variety of cell biological, biochemical, and biophysical techniques will be used.